Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term inhalative toxicity data is available for FAT40868; therefore, anticipating comparable absorption by inhalative and oral route (both 10% assumed), a NOAEC corr of 1000 mg/kg/day / 0.38 m³/kg * 6.7/10 * 10%/10% = 1763 mg/m³ is used.

AF for dose response relationship:
1
Justification:
not required as starting point is NOAEC corr.
AF for differences in duration of exposure:
2
Justification:
default value for sub-chronic study data
AF for interspecies differences (allometric scaling):
1
Justification:
not required due to route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
default factor for remaining differences
AF for intraspecies differences:
5
Justification:
for worker, a default AF of 5 is to be used
AF for the quality of the whole database:
1
Justification:
not required, available data fulfill scientific principles
AF for remaining uncertainties:
1
Justification:
not required, no other uncertainties need to be considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification required from oral to dermal, as for both routes equivalent absorption (both 10%) is assumed and therefore no correction is applied.

AF for dose response relationship:
1
Justification:
NOAEL was used as the starting point
AF for differences in duration of exposure:
2
Justification:
based on a sub-chronic study result
AF for interspecies differences (allometric scaling):
4
Justification:
rats were used in tests
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data was available
AF for intraspecies differences:
5
Justification:
default factor for workers
AF for the quality of the whole database:
1
Justification:
not required, available data fulfill scientific principles
AF for remaining uncertainties:
1
Justification:
not required, no other uncertainties need to be considered
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

There is no available toxicity data concerning the test substance on humans.

In a sub-chronic toxicity study, the test substance was administered daily by oral gavage to Wistar rats of both sexes at dose levels of 0, 10, 100 and 1000 mg/kg body weight/day for a period of 90 days. No adverse treatment-related effects were noted on any parameter observed during the study. 1000 mg/kg body weight/day of the test item was established as the no-observed-adverse-effect-level (NOAEL).

Another available report was conducted according to OECD guideline 421 under GLP condition. FAT 40868 was administered by daily oral gavage to male and female Wistar rats at dose levels of 100, 300 and 1000 mg/kg, also showing no adverse treatment related effects and establishing to NOAEL in this study at 1000 mg/kg bw/d too for parental toxicity and reproductive toxicity being in a good agreement with the results from the 90-day repeated dose toxicity study (see above).

Studies on acute oral and acute dermal toxicity at dosing up to 2000 mg/kg bw showed no treatment related effects and neither were effects seen on skin and eye irritation in in vitro and in vivo studies. In a LLNA study for skin sensitisation (OECD 429), skin sensitising effects were seen at 10, 25 and 50% concentration. Thus, the substance is considered a skin sensitiser. Three in vitro studies for mutagenicity were negative.

The toxicological data above were taken into account for DNEL derivation as described.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
870 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term inhalative toxicity data is available for FAT40868; therefore, anticipating comparable absorption by inhalative and oral route (both 10% assumed), a NOAEC corr of 1000 mg/kg/day / 1.15 m³/kg * 10%/10% = 870 mg/m³ is used.

AF for dose response relationship:
1
Justification:
NOAEC is used as the starting point
AF for differences in duration of exposure:
2
Justification:
based on the sub-chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not applied for derivation of inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
no other substance-specific effects are available
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
not required, available data fulfill scientific principles
AF for remaining uncertainties:
1
Justification:
not required, no other uncertainties need to be considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modification required from oral to dermal, as for both routes equivalent absorption (both 10%) is assumed and therefore no correction is applied.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point
AF for differences in duration of exposure:
2
Justification:
based on the sub-chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
rats were used
AF for other interspecies differences:
2.5
Justification:
no other substance-specific data are available
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
available data fulfill the scientific requirements
AF for remaining uncertainties:
1
Justification:
no other uncertainties need to be considered
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point
AF for differences in duration of exposure:
2
Justification:
based on the sub-chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
rats were used
AF for other interspecies differences:
2.5
Justification:
no other substance-specific effects are available
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
available data fulfill the scientific requirements
AF for remaining uncertainties:
1
Justification:
no other uncertainties need to be considered
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

See description of relevant data in section on workers.